Assessment of gastric cancer malignancy based on CD133 and thrombospondin1 (THBS1) expression and the role of histone acetylation.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 31-31
Author(s):  
Hirohiko Sato ◽  
Mitsuo Shimada ◽  
Nobuhiro Kurita ◽  
Takashi Iwata ◽  
Masanori Nishioka ◽  
...  

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Menghui Wu ◽  
Yuchen Pan ◽  
Zhifang Jia ◽  
Yueqi Wang ◽  
Na Yang ◽  
...  

Background. Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods. Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results. The patients were classified according to a Fib-Alb score of 0 (n=376), 1 (n=327), or 2 (n=139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P=0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P=0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P=0.001) was a significant independent predictive factor for RFS. Conclusions. The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
Yuji Toiyama ◽  
Yasuhiro Inoue ◽  
Takahito Kitajima ◽  
Tadanobu Shimura ◽  
Hiroki Imaoka ◽  
...  

9 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and is known to act as a causative mediator of chronic inflammation and inflammatory carcinogenesis. Recently, we demonstrated that ANGPTL2 overexpresses in gastric cancer (GC) compared to normal gastric mucosa and high ANGPTL2 is associated with poor prognosis. Therefore, if tumor-derived ANGPTL2 over-secretes systemically, focusing ANGPTL2 in blood is logical to evaluate its ability as a biomarker. Accordingly, we quantified serum ANGPTL2 level and assessed its clinical significance in GC patients. Methods: We screened serum ANGPTL2 levels from 32 GC and 24 normal controls (NC) by ELISA (cohort 1). Next, we validated 194 serum samples from GC and 48 NC (cohort 2). Finally, we examined ANGPL2 expression in matched GC tissues of cohort 2 (n=194) by immunohistochemistry (IHC). The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: In cohort 1,serum ANGPTL2 levels in GC were significantly higher than that in NC (p<0.05). Serum ANGPTL2 differentiated GC from NC with high accuracy (AUC=0.814). Analysis of cohort 2 also indicated that serum ANGPTL2 levels in GC were significantly higher compared to NC (p<0.0001), and increased according to UICC stage progression. In addition, serum ANGPTL2 had a promising AUC (0.831) with high sensitivity (73.0%) and specificity(82.2%) to distinguish GC from NC. High serum ANGPTL2 was significantly associated with lymphatic invasion (p=0.03), vessel invasion (p=0.02), distant metastases (p=0.0002), early recurrence (p=0.004) and poor survival (p=0.01), consequently emerged as an independent predicting recurrence marker (HR=5.06, p=0.0004) and prognostic marker (HR=3.6, p=0.01) in GC. Of interest, ANGPTL2 levels in serum from GC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 at the invasive margin of matched GC tissues (r= 0.16, p=0.02). Conclusions: Serum ANGPTL2 levels, which might be secreted from primary or metastatic site into blood stream, have extremely strong potential as a novel biomarker for diagnosis, predicting recurrence and poor prognosis in GC patients.


2020 ◽  
Vol 9 (5) ◽  
pp. 1275
Author(s):  
Won Hyuk Choi ◽  
Min Jeong Kim ◽  
Jun Ho Park ◽  
Jin Gu Kang ◽  
Seung In Seo ◽  
...  

(Background) The aim of this study was to investigate the prognostic impact of lymphatic invasion in gastric cancer, focusing on survival differences between N stage groups. (Methods) A total of 398 consecutive patients who underwent curative gastrectomy for primary gastric adenocarcinoma from January 2006 to December 2015 were analyzed retrospectively using data from a prospectively collected registry database. We compared various clinicopathological features and survival differences between lymphatic invasion-positive and -negative groups. (Results) Of the 398 patients, 141 (35.4%) showed lymphatic invasion. The lymphatic invasion-positive subgroup had poorer prognosis than the lymphatic invasion-negative subgroup in N0 (five-year survival rate: 87.8% vs. 73.6%, p = 0.048) and N1 (87.2% vs. 50%, p = 0.007) stage patients. The odds ratio (OR) of lymphatic invasion to five-year survival rate was 2.078 (95% confidence interval (CI), 1.103–3.916; p = 0.024). The presence of lymphatic invasion had worse effect on survival than age (OR, 1.807; 95% CI, 1.024–2.242; p = 0.029) or tumor depth (OR, 1.286; 95% CI, 1.078–1.897; p = 0.013) in N0 and N1 stage patients. The overall survival of patients with lymphatic invasion was not different from that of patients at a one-higher N stage without lymphatic invasion at any N stage. (Conclusions) The presence of lymphatic invasion may be the most important independent prognostic factor in N0 and N1 gastric cancer and might be an upstaging factor of N stage at any N stage. Therefore, in addition to the number of metastasized lymph nodes, the presence of lymphatic invasion should be included in N stage determination.


Mastology ◽  
2021 ◽  
Vol 31 ◽  
Author(s):  
Ana Cláudia Leite Vilela ◽  
Lucimara Priscila Campos Veras ◽  
Sérgio Eduardo Paiva Ramos ◽  
Sádia Martins de Paula Souza

Introduction: Breast cancer is a relevant public health issue, and its incidence has increased in patients aged less than 50 years. This population usually receives a late diagnosis, which contributes with the poor prognosis of the condition. Objective: To assess the percentage of patients diagnosed with breast cancer before the age of 50 and compare them with the group that was diagnosed after the age of 50. Results: The general mean age was 54 years; 75.68% of the patients were younger than 50 years, aged between 40 and 49 years. Among the ones who were younger than 50, 35.14% were in stage T4; 55.41% underwent neoadjuvant chemotherapy; 16.22% presented distant metastasis; and 10.81%, locoregional metastasis. On the other hand, among those aged more than 50, 22.71% were in stage T4; 30.68% underwent neoadjuvant chemotherapy; 11.36% presented distant metastasis; and 6.82%, locoregional metastasis. Conclusion: Breast cancer in women aged less than 50 years in a Mastology service in the Federal District has been a matter of concern, for presenting more advanced tumors at the time of diagnosis; screening is still debatable.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 96-96
Author(s):  
Joji Kitayama ◽  
Hironori Ishigami ◽  
Hironori Yamaguchi ◽  
Shigenobu Emoto ◽  
Toshiaki Watanabe

96 Background: A new regimen of intravenous (IV) and intraperitoneal (IP) Paclitaxel (PTX) combined with oral S-1 is effective as the first line chemotherapy for gastric cancer with peritoneal metastasis. However, no information is available for the benefit of gastrectomy at salvage setting for the patients with clinical downstage. Methods: A total of 100 patients with peritoneal metastasis of gastric cancer received combination chemotherapy of PTX from both IV (50 mg/m2) and IP (20 mg/m2) routes using subcutaneous implanted peritoneal access ports at on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Gastrectomy was performed in 60 patients who showed apparent shrinkage of peritoneal nodules as well as negative peritoneal cytology at 2nd look laparoscopy. In 30 of the 60 patients with gastrectomy, mRNA of carcinoembryonic antigen (CEA) in peritoneal lavages obtained from the port were quantitatively evaluated by CEA-mRNA Index (CmRI: CEA mRNA/ PBGD mRNA×104) at each chemotherapeutic cycle. Results: MST of the 100 patients was 23.5 months. MST and 1y-OS of the 60 patients with gastrectomy were 34.5 months and 83%, while those of the other 40 patients were 13.0 months and 39%, respectively. In all of the 30 gastrectomized patients, CmRI at the initial laparoscopy was considerably high (median=15368, 145-398179), which was fairly reduced after 3 courses of the combination chemotherapy before surgery (median=25, 0-10286, p=<0.001). Among them, 2y-OS of 22 patients whose CmRI was reduced to the value <200 after 3 course of chemotherapy was significantly better than that of the other 8 patients with CmRI >200 (76% vs 25% p=0.02), suggesting the volume of tumor cells in peritoneal cavity may be a critical determinant for postoperative outcome. Conclusions: Combination chemotherapy of S-1 plus IV and IP PTX followed by gastrectomy is a promising strategy for peritoneal metastasis of gastric cancer. Periodical measurement of CEA-mRNA levels in peritoneal cavity can be a useful biomarker to predict the clinical efficacy of conversion gastrectomy.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 125-125
Author(s):  
Dexter Yak Seng Chan ◽  
Nicholas Syn ◽  
Cui Ting Neogh ◽  
Niam Sin Phua ◽  
Elya . ◽  
...  

125 Background: Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a grave prognosis. Studies have shown increased drug concentration in the peritoneal cavity when chemotherapy is administered intraperitoneally (IP). We had previously published early results on IP paclitaxel plus XELOX for such patients and now present our longer term data. Methods: Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology, not previously-treated or received prior systemic therapy > 180 days ago and ECOG ≤2 are eligible. Patients were treated with 8 cycles of paclitaxel 40 mg/m2 IP on days 1 and 8, oxaliplatin 100 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 b.i.d. PO for 2 weeks followed by 1 week of rest. The primary endpoint is 1-year overall survival rate and the secondary endpoints are safety, response rate and peritoneal cytological response. Patients who subsequently have no distant metastases, with stable or reduced peritoneal disease and 2 consecutive negative peritoneal cytology would be eligible for conversion gastrectomy. Results: 34 patients have been enrolled and received at least one cycle at the time of reporting. Median no. of cycles is 8 (range: 1–8) and median follow-up is 30.2 months. Median OS is 16.4 months (IQR: 10.1–27.2) and 1-year survival rate is 64.9% (95% CI: 45.5%–78.9%). Of 30 evaluable patients, 1 achieved CR (3.3%), 6 (20.0%) achieved PR, 16 (53.3%) achieved SD and 7 (23.3%) experienced PD. Peritoneal cytology turned negative in 17 of 32 (53.1%) patients. Severe (grade ≥ 3) AE were neutropenia ( N= 7), febrile neutropenia ( N= 3), diarrhoea ( N= 3), hand-foot syndrome ( N= 2), bacterial peritonitis ( N= 2) and hypokalaemia ( N= 4) and tumour perforation ( N= 1). One death occurred due to neutropenic sepsis. 8 patients had conversion gastrectomy with no additional morbidity, with a 1-year survival of 87.5% with a median OS of 18.8 months. Conclusions: XELOX + IP paclitaxel appears to be a well-tolerated and active regimen in gastric cancer with peritoneal metastases, and may offer survival benefits. Finally, conversion gastrectomy may be considered in patients with favourable response. Clinical trial information: NCT01739894.


Author(s):  
Keigo Yamamichi ◽  
Yoshihiko Uehara ◽  
Naomi Kitamura ◽  
Yasushi Nakane ◽  
Koshiro Hioki

Author(s):  
Bruno José Queiroz Sarmento ◽  
Alexandre Menezes Brito ◽  
Daniela Medeiros Milhomem Cardoso ◽  
Paulo Moacir de Oliveira Campoli ◽  
Osterno Queiroz da Silva ◽  
...  

BACKGROUND: An important aspect dealing with gastric cancer is the role of lymphadenectomy in gastric cancer staging. AIM: To verify if lymphadenectomy with stations separation increases the number of dissected lymph nodes and establish comparison between TNM 2002 and JGCA 1998 evaluating lymph nodal status (N). METHODS: This is a retrospective analysis of the patients that underwent curative gastrectomy and D2 dissections for adenocarcinoma between 2004 and 2006. Between January of 2004 and June of 2005 (group 1), lymphadenectomy was performed en-bloc with gastrectomy and only TNM system was used. After June of 2005 (group 2), the surgeon himself dissected lymph nodal stations, allowing use of TNM and JGCA systems. Studied aspects were age, Borrmann classification, histological grade, venous or lymphatic invasion, depth of invasion, peritoneal cytology and type of gastrectomy. End points were number of dissected lymph nodes, number of positive lymph nodes and agreement between staging systems. Chi-square test and T-test were used for statistical analysis. RESULTS: One hundred forty-five gastrectomies were performed, 76 in group 1 and 69 in group 2. In group 1, mean age was of 61 years and 59 years in group 2 (P=0,12). Eighty per cent of tumors were advanced in both groups. Venous or lymphatic invasion and positive peritoneal cytology were more frequent in group 1, 65.6% vs 35,3% (P= 0,001) e 13.9% vs 3.1% (P=0,03), respectively. Borrmann classification, histological grade, Lauren classification and type of gastrectomy were not different between the groups. In group 1, mean number of lymph nodes was 32,7 and 37,35 in group 2 (P= 0,09). Rates of positive lymph nodes in groups 1 and 2 were 72.2% and 53%, respectively (P= 0,02). Migration analysis of lymph node status (N) realized only in group 2 (69 patients) showed agreement between TNM and JGCA in 50 patients (72,5%). Using JGCA system, modification in 19 patients occurred (27,5%), with upstaging in 13 (18,8%) and downstaging in six (8,7%). CONCLUSION: In this study, a tendency of increase in number of lymph nodes was verified when the surgeon himself dissected lymph nodal stations. JGCA system modified the lymph nodal staging in comparison to TNM system in 30% of all cases.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21012-21012
Author(s):  
K. Miyake ◽  
M. Shimada ◽  
S. Imura ◽  
K. Sugimoto ◽  
E. Batmunkh ◽  
...  

21012 Background: Hypoxia-inducible factor-1a (HIF-1a) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1a expression, however, the association between HIF-1a and histone deacetylase 1 (HDAC1) / metastasis-associated protein 1 (MTA1) is not fully understood. Here, we explored the involvement of HIF-1a and HDAC1/MTA1 in human pancreatic carcinoma. Methods: HIF-1a, HDAC1 and MTA1 expressions were detected by immunohistochemistry in surgical specimens obtained from 39 patients with pancreatic carcinoma. The correlations between the expression of HIF-1a, HDAC1 or MTA1 and clinical features, and the prognosis of patients with pancreatic carcinoma were then analyzed. Results: HIF-1a, HDAC1 and MTA1 positive stainings were found in 16 of 39 cases (41%), 22 of 39 cases (56%) and 12 of 39 cases (31%), respectively. There was no correlation between HIF-1a, HDAC1 or MTA1 expression levels and any of the clinical parameters examined. The five-year survival rate for pancreatic carcinoma patients with HIF-1a and HDAC1 positive stainings were significantly lower than for those patients with HIF-1a and HDAC1 negative stainings (P = 0.0243 and 0.0433). The MTA1 positive stainings group did not have a significantly worse prognosis than the MTA1 negative stainings group (P = 0.9694). In addition, the five-year survival rate for the HDAC1/MTA1 positive stainings group was statistically significantly worse than for the other groups (P = 0.0386). Conclusions: These results suggest that HIF-1a expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis on human pancreatic carcinoma, and indicate that HIF-1a and HDAC1/MTA1 is a promising therapeutic target in pancreatic carcinoma treatment. No significant financial relationships to disclose.


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